The purpose of this project is to study the physical, chemical, and ultrastructural properties of calcium phosphate salts, and to clarify the kinetic and thermodynamic processes and the interactions with substances of biological interest that uniquely enable calcium phosphate salts to carry out their specialized role in vivo. The properties of calcium phosphate salts are being studied with a variety of ultrastructural and physical-chemical techniques such as electron microscopy, x-ray diffraction, surface area analyses, chromatographic and standard analytical chemistry procedures. The principal endeavor currently being pursued involves artificial lipid vesicles (liposomes) as in vitro models to investigate physico-chemical aspects of matrix vesicle (MV)-mediated calcification in vivo. The latest phase of this endeavor is a study that is examining the effect that organic phosphonates have on mineral development in the liposomal model system. The aim of this study is to better delineate the physicochemical basis for the observed suppressive effects bisphosphonates have on biological calcification. Findings from this study showed that when present in the external suspension solution, the investigated phosphonates did not delay the initial formation of apatitic calcium phosphate salts within the liposomes, nor the penetration of the crystals through the enclosing membranes. However, they variably retarded subsequent growth and proliferation once the crystals were released into the suspending medium. The effectiveness of the phosphonates in inhibiting extraliposomal precipitation is strongly dependent upon their structure, with geminal bisphosphonates having the greatest negative impact. The results suggest that inhibitory binding to crystal growth sites was strongest when the phosphonate molecule contained two phosphonic groups linked to the same carbon atom. The effectiveness of non-geminal bisphosphonates depended upon the presence of electron withdrawing groups, e.g. keto groups, in positions a to the phosphonic groups.